For proper functioning of the lens, elasticity and clarity are of paramount importance. These characteristics are dependent on the integrity of the lens capsule basement membrane and the lens crystallins. The system for their synthesis and maintenance is knwon to be delicate, however, and can often be disrupted in many diseases, generally leading to lens cataracts. Diabetes mellitus is one such disease that has cataractous tendencies and also is known to alter basement membranes, both structurally and functionally. We intend to study the basement membrane and crystallins of the lens and investigate how these proteins are affected by diabetes and cataracts. We will establish cell lines from human normal, diabetic, and cataractous lens epithelium, as well as appropriate mouse models of these epithelia in monolayer tissue culture. This will provide us with large quantities of biosynthetic products for direct biochemical and immunological study without the need for harsh extraction procedures. By use of somatic cell hybridization, we will investigate the genetic control of basement membrane and crystallin biosynthesis, and carry out gene mapping of the chromosomes responsible for the proteins and their processing enzymes. Furthermore, hybrids produced between normal x diseased, and diseased x diseased lens cells will give much insight into the mechanisms and controls that function in the biosynthesis of lens proteins. These data will help define the true nature of the lens and further help to establish a biochemical basis for symptoms seen in these disease states.